Is CCT8 p.Lys400Arg (c.1199A>G) pathogenic?

CCT8 p.Lys400Arg (c.1199A>G) is classified Uncertain significance in CCT8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.1215); Very rare (popmax 0.00267%, afr).

How common is CCT8 p.Lys400Arg (c.1199A>G) in the general population?

CCT8 p.Lys400Arg (c.1199A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CCT8 p.Lys400Arg (c.1199A>G)?

AlphaMissense predicts likely benign (score 0.1215) — an in-silico prediction, not a clinical call.

CCT8 p.Lys400Arg

c.1199A>G · VCV3829302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1215 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1215	likely benign
REVEL	0.655	pathogenic-leaning
SaProt	LLR -6.40	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 17 kb · p 9.2e-05 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,784 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000684% 11/1,608,080 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00322%	31,083
African / African-Americangrpmax	0.00267%	37,392
East Asian	0.00223%	44,864
South Asian	0.0022%	45,460
European (non-Finnish)	0.00034%	293,993

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CCT8
Protein: p.Lys400Arg
Coding: c.1199A>G
MANE Select: NM_006585
Type: single nucleotide variant
Location: chr21:29062141 (GRCh38)
Gene constraint: LOEUF 0.287 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.85 · 71 PDB
Residue 400: a modified residue (n6-acetyllysine); an α-helix

Full CCT8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCT8 p.Val409Ile Benign ★★ same type
CCT8 p.Ala12Thr Uncertain significance ★ ⚠ same type
CCT8 p.Ala186Thr Uncertain significance ★ ⚠ same type
CCT8 p.Ala298Thr Uncertain significance ★ ⚠ same type
CCT8 p.Ala35Thr Uncertain significance ★ ⚠ same type
CCT8 p.Ala442Gly Uncertain significance ★ ⚠ same type
CCT8 p.Ala447Val Uncertain significance ★ ⚠ same type
CCT8 p.Ala451Thr Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cct8-p-lys400arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown